We confirmed direct binding of recombinant hnRNPK to GAP17 exon 17, with similar affinity to a previously established hnRNPK target ( Figures 3I and S4J). Transcripts whose splicing was similarly regulated by p53 R175H and hnRNPK included GAP17 and GAP12, both of which underwent hnRNPK-promoted inclusion of pol圜 exons. Indeed, splicing changes induced by p53 R175H in these same cells were also induced by hnRNPK (Fisher's exact test p < 0.0001, Figure 3H Table S5). Importantly, exons promoted by hnRNPK were enriched in C-rich sequences while exons repressed by hnRNPK knockdown were enriched in purines ( Figure 3G), mirroring the sequence-specific splicing changes induced by p53 R175H. As in the case of p53 R175H, knockdown of hnRNPK significantly altered exon splicing ( Figure S4I Table S5). Genetic end‐points 2.2.2.1 Point mutation 2.2.2.2 Recombination 2.2.2.To determine whether hnRNPK mediated the splicing changes promoted by p53 R175H, we silenced hnRNPK in p53 R172H-mutant PDAC cells ( Figure 3F and S4H) and performed RNA-seq. Genotoxicity studies using yeast cultures 2.2.1. Discussion 2.1.5.1 How the most critical factors identified above can influence the validity of the data 2.1.5.2 Interpretation of the results in terms of the intrinsic mutagenic activity of the test material 2.2. Presentation and interpretation of data 2.1.4.1 Data‐processin g and presentation 2.1.4.2 Interpretation of data in terms of positive and negative 2.1.4.3 Dealing with ambiguous results 2.1.5. The procedure 2.1.3.1 Outline of the basic procedure 2.1.3.2 Critical factors in the procedure 2.1.4. Relevance and limitations of the assay 2.1.3. Principles and scientific basis of the assay 2.1.2. DESCRIPTION OF WIDELY‐ADOPTED PROCEDURES 2.1. CONTENTS GUIDE TO SHORT‐TERM TESTS FOR DETECTING MUTAGENIC AND CARCINOGENIC CHEMICALS PREAMBLE 1. Errors and omissions excepted, the names of proprietary products are distinguishe d by initial capital letters. The mention of specific companies or of certain manufacturers ' products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the Secretariat of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. World Health Organization 1985 Publications of the World Health Organization enjoy copyright protection in accordance with the provisions of Protocol 2 of the Universal Copyright Convention. Other activities carried out by the IPCS include the development of know‐how for coping with chemical accidents, coordination of laboratory testing and epidemiologica l studies, and promotion of research on the mechanisms of the biological action of chemicals. Supporting activities include the development of epidemiologica l, experimental laboratory, and risk‐assessm ent methods that could produce internationa lly comparable results, and the development of manpower in the field of toxicology. The main objective of the IPCS is to carry out and disseminate evaluations of the effects of chemicals on human health and the quality of the environment. Published under the joint sponsorship of the United Nations Environment Programme, the International Labour Organisation, and the World Health Organization World Health Orgnization Geneva, 1985 The International Programme on Chemical Safety (IPCS) is a joint venture of the United Nations Environment Programme, the Internationa l Labour Organisation, and the World Health Organization. This report contains the collective views of an international group of experts and does not necessarily represent the decisions or the stated policy of the United Nations Environment Programme, the International Labour Organisation, or the World Health Organization.
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